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Background: A novel 10-day sequential treatment regimen recently achieved a significantly higher eradication rate than standard 7-day therapy in both peptic ulcer disease and non-ulcer dyspepsia. Its higher performance has recently been confirmed using a halved clarithromycin dose in peptic ulcer disease. Aims: To evaluate whether an acceptable eradication rate could also be obtained by halving the clarithromycin dose in dyspeptic patients and to assess the role of possible factors affecting the outcome of therapy. Methods: In a prospective, open-label study, 162 patients with non-ulcer dyspepsia and Helicobacter pylori infection, assessed by rapid urease test and histology, were enrolled. Patients were randomized to receive either 10-day sequential therapy, comprising rabeprazole 20 mg b.d. plus amoxicillin 1 g b.d. for the first 5 days, followed by rabeprazole 20 mg b.d., clarithromycin 250 mg b.d. and tinidazole 500 mg b.d. for the remaining 5 days (low-dose therapy), or a similar schedule with clarithromycin 500 mg b.d. (high-dose therapy). Four to six weeks after therapy, H. pylon eradication was assessed by endoscopy/histology. Results: A similar H. pylon eradication rate was observed following low- and high-dose regimens for both per protocol (94% vs. 95%; P = N.S.) and intention-to-treat (93% vs. 94%; P = N.S.) analyses. No major side-effects were reported. Halving the clarithromycin dose leads to a per patient saving in pharmaceutical costs of 24.6 euros. None of the variables examined affected the effectiveness of eradication of the sequential regimen. Conclusion: A reduction of the clarithromycin dose does not affect H. pylon eradication with the sequential regimen in non-ulcer dyspepsia and affords lower costs. [ABSTRACT FROM AUTHOR]

A retrospective analysis was conducted to investigate how a bright luminal sign on high b-value diffusion-weighted imaging (DWI) could be considered as a new biomarker for identifying fibrotic strictures in Crohn's disease (CD). Fibrotic strictures, due to excessive deposition of extracellular matrix following chronic inflammatory processes, can be difficult to distinguish from inflammatory strictures using endoscopy. This study was performed on 65 patients with CD who underwent MRE, and among them 32 patients showed the bright luminal sign on high b-value DWI. DWI findings were compared to pre- and post-contrast MRE data. Luminal bright sign performance results were calculated using a confusion matrix, the relationship between categorical variables was assessed by the χ2 test of independence, and the Kruskal-Wallis test (ANOVA) was used for the assessment of statistical significance of differences between groups. The results indicated a high sensitivity (90%) and specificity (85%) of the bright luminal sign for fibro-stenotic CD and a significant correlation between DWI luminal brightness and markers such as the homogeneous enhancement pattern ( p < 0.001), increase in enhancement percentage from 70 s to 7 min after gadolinium injection ( p < 0.001), and submucosal fat penetration ( p = 0.05). These findings indicate that DWI hyperintensity can be considered as a good non-invasive indicator for the detection of severe intestinal fibrosis and may provide an efficient and accurate method for assessing fibrotic strictures. This new non-invasive biomarker could allow an early diagnosis of fibrotic stricture, delaying the onset of complications and subsequent surgery. Moreover, further evaluations through larger prospective trials with histopathological correlation are needed to confirm these results and completely determine the clinical benefits of DWI in treating CD.

Incentivising prosocial and pro-environmental behaviours is a sensitive endeavour. While behavioural change is urgently needed to mitigate the consequences of climate change, monetary interventions often have negative side effects. Such interventions are prone to motivation crowding, which can impede lasting positive behavioural change and stimulate negative temporal spillovers to other prosocial behaviours. In this study, we investigate whether implementing monetary interventions as part of policy mixes can mitigate these negative side effects. In an online experiment involving 3782 participants, we test whether the use of nudges that make personal and social norms salient can counteract the motivation-crowding effect and explore the effects of such policy mixes on temporal spillovers. We find that policy mixes of norm-based nudges and monetary incentives are more effective at stimulating engagement in targeted prosocial behaviour than no intervention when controlling for sample characteristics. Analysing the temporal spillover effects of these interventions reveals that policy mixes can alleviate the tendency of monetary incentives to negatively affect subsequent prosocial behaviour. This indicates that norm-based nudges are suitable complements to monetary interventions, facilitating long-lasting positive effects., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Ustekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist recently approved for treating ulcerative colitis (UC) but with limited real-world data. Therefore, we evaluated the effectiveness and safety of UST in patients with UC in a real-world setting., Research Design and Methods: This is a multicenter, retrospective, observational cohort study. The primary endpoints were the clinical remission rate (partial Mayo score, PMS, ≤1) and the safety of UST. Other endpoints were corticosteroid-free remission (CSFR) rate, clinical response rate (PMS reduction of at least 2 points), and fecal calprotectin (FC) reduction at week 24., Results: We included 256 consecutive patients with UC (M/F 139/117, median age 52). The clinical remission and clinical response rates at eight weeks were 18.7% (44/235) and 53.2% (125/235), respectively, and 27.6% (42/152) and 61.8% (94/152) at 24 weeks, respectively. At 24 weeks, CSFR was 20.3% (31/152), and FC significantly dropped at week 12 ( p  = 0.0004) and 24 ( p  = 0.038). At eight weeks, patients naïve or with one previous biologic treatment showed higher remission ( p  = 0.002) and clinical >response rates ( p  = 0.018) than patients previously treated with ≥ 2. Adverse events occurred in six patients (2.3%), whereas four patients (1.6%) underwent colectomy., Conclusion: This real-world study shows that UST effectively and safely treats patients with UC.

Background: Data regarding the real-world (RW) use of tofacitinib (TOF) in patients with ulcerative colitis (UC) are limited. We aimed to investigate TOF's RW efficacy and safety in Italian UC patients., Research Design and Methods: A retrospective assessment of clinical and endoscopic activity was performed according to the Mayo score. The primary endpoints were to evaluate the effectiveness and safety of TOF., Results: We enrolled 166 patients with a median follow-up of 24 (IQR 8-36) weeks. Clinical remission was achieved in 61/166 (36.7%) and 75/166 (45.2%) patients at 8-week and 24-week follow-ups, respectively. The optimization was requested in 27 (16.3%) patients. Clinical remission was achieved more frequently when TOF was used as a first/second line rather than a third/fourth line treatment ( p  = 0.007). Mucosal healing was reported in 46% of patients at the median follow-up time. Colectomy occurred in 8 (4.8%) patients. Adverse events occurred in 12 (5.4%) patients and severe in 3 (1.8%). One case of simple Herpes Zoster and one of renal vein thrombosis were recorded., Conclusions: Our RW data confirm that TOF is effective and safe in UC patients. It performs remarkably better when used as the first/second line of treatment.

Carbon pricing can steer energy choices towards low-carbon fuels and foster energy conservation efforts. Simultaneously, higher fossil fuel prices may exacerbate energy poverty. A just portfolio of climate policies therefore requires a balanced instrument mix to jointly combat climate change and energy poverty. We review recent policy developments in the EU aimed at addressing energy poverty and the social implications of the climate neutrality transition. We then operationalise an affordability-based definition of energy poverty and numerically illustrate that recent EU climate policy proposals risk raising the number of energy poor when not accompanied with complementary measures, while alternative climate policy designs could lift more than 1 million households out of energy poverty through income-targeted revenue recycling schemes. While these schemes have low informational requirements and appear sufficient to avoid exacerbating energy poverty, the findings suggest that more tailored interventions are needed. Finally, we discuss how insights from behavioural economics and energy justice can help shape optimal policy packages and processes., (© 2023. The Author(s).)

Background: Vedolizumab (VDZ) can be used to treat refractory ulcerative colitis (UC) and Crohn's disease (CD). We assessed whether there are differences in treating UC vs CD with VDZ., Research Design and Methods: Mayo score in UC and the Harvey-Bradshaw Index (HBI) in CD scored the clinical activity. Achievement and maintenance of clinical remission during the follow-up, and safety were the primary endpoints., Results: 729 patients (475 with UC and 254 with CD), median follow-up of 18 (IQR 6-36) months, were enrolled. Clinical remission at the 6 th month of treatment was achieved in 488 (66.9%) patients (74.4% in CD vs 62.9% in UC, p<0.002) while, during the follow-up, no difference was found (81.5% in the UC group and 81.5% pts in the CD group; p=0.537). The clinical remission at the 6 th month of treatment (p=0.001) and being naïve to biologics (p<0.0001) were significantly associated with prolonged clinical remission. The clinical response was significantly higher in UC (90.1%) vs CD (84.3%) (p=0.023), and surgery occurred more frequently in CD (1.9% in UC vs 5.1% in CD, p=0.016)., Conclusion: We found differences when using VDZ in UC vs CD in real life. These parameters can help the physician predict this drug's longterm efficacy.

Background: Adalimumab (ADA) biosimilars have entered the therapeutic armamentarium of inflammatory bowel disease (IBD), allowing for the treatment of a greater number of patients for their reduced cost than the originator. However, comparative data on the efficacy and safety of the various ADA biosimilars remains scarce.We compare the efficacy and safety of ADA biosimilars SB5, ABP501, GP2017, and MSB11022 in treating IBD outpatients in a real-life Italian setting., Methods: A retrospective analysis was performed on consecutive IBD outpatients with complete clinical, laboratory, and endoscopic data. Clinical activity was measured using the Mayo score in ulcerative colitis (UC) and the Harvey-Bradshaw Index in Crohn's disease (CD). The primary endpoints were the following: (1) induction of remission in patients new to biologics and patients new to ADA but previously exposed to other anti-tumor necrosis factor agents or other biologics; (2) maintenance of remission in patients switched from the ADA originator to an ADA biosimilar; and (3) safety of various biosimilars., Results: A total of 533 patients were enrolled according to the inclusion criteria: 162 patients with UC and 371 patients with CD. Clinical remission was obtained in 79.6% of patients new to biologics and 59.2% of patients new to ADA but not to other biologics; clinical remission was maintained in 81.0% of patients switched from the originator, and adverse events were recorded in 6.7% of patients. There was no significant difference between the 4 ADA biosimilars for each predetermined endpoint., Conclusions: Adalimumab biosimilars are effective and safe in IBD treatment, both in new patients and in patients switched from the ADA originator. No difference in efficacy and safety was found between ADA biosimilars., (© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: Adalimumab (ADA) biosimilars have been included into the therapeutic armamentarium of inflammatory bowel disease (IBD); however, comparative data on the efficacy and safety of the different ADA biosimilars after replacing the ADA originator for a non-medical reason remains scarce. We aimed to compare in a real-life setting the efficacy and safety of four ADA biosimilars SB5, APB501, GP2017, and MSB11022 in IBD patients after replacing the originator for a non-medical reason., Methods: A multicenter retrospective study was performed on consecutive IBD patients, analyzing clinical, laboratory, and endoscopic data. The primary endpoints of the study were maintenance of clinical remission and safety of the different biosimilars., Results: 153 patients were enrolled, 26 with UC and 127 with CD. Clinical remission was maintained in 124 out of 153 (81%) patients after a median (IQR) follow-up of 12 (6-24) months, without any significant difference between the four ADA biosimilars. ADA biosimilars dosage was optimized in five patients (3.3%). Loss of remission was significantly higher in UC patients (10/26 patients, 38.5%) than in CD patients (19/127 patients, 14.9%, p<0.025). Adverse events occurred in 12 (7.9%) patients; the large majority were mild., Conclusions: No difference in efficacy and safety was found between ADA biosimilars when used to replace the ADA originator for a non-medical reason. However, in UC patients the replacement of ADA originator for this reason should be carefully assessed.

Background: To compare the performances of Infliximab (IFX) biosimilar CT-P13 and SB2 in the treatment of Inflammatory Bowel Diseases (IBD) outpatients in Italy., Research Design and Methods: Three hundred and eighty IBD outpatients were retrospectively evaluated. The primary endpoint was to compare the two IFX biosimilars in terms of reaching and maintenance of remission at any timepoint., Results: 197 patients with Ulcerative Colitis (UC) and 183 patients with Crohn's Disease (CD) treated with CT-P13 or SB2 and having a median (IQR) follow-up of 12 (6-36) months were compared: 230 (60.5%) were naïve to anti-TNFα, 20 (5.26%) were switched from IFX originator or from IFX CT-P13 to IFX SB2. Clinical remission was achieved in 133 (67.5%) UC patients and in 164 (89.6%) CD patients (p < 0.000), with no differences between CT-P13 and SB2 in the rate of remission in UC (p = 0.667) and CD (p = 0.286). Clinical response, steroid-free remission, rate of surgery, mucosal healing (MH) in UC, switching from IFX originator or from other biosimilar, and safety were similar. Higher MH rate was obtained in CD patients treated with CT-P13 (p = 0.004)., Conclusion: This first comparative study found that both IFX biosimilars CT-P13 and SB2 are effective and safe in managing IBD outpatients.

Background and Aims: Several studies have found Golimumab (GOL) effective and safe in the short-term treatment of ulcerative colitis (UC), but few long-term data are currently available from real world. Our aim was to assess the long-term real-life efficacy and safety of GOL in managing UC outpatients in Italy., Methods: A retrospective multicenter study assessing consecutive UC outpatients treated with GOL for at least 3-month of follow-up was made. Primary endpoints were the induction and maintenance of remission in UC, defined as Mayo score ≤2. Several secondary endpoints, including clinical response, colectomy rate, steroid free remission and mucosal healing, were also assessed during the follow-up., Results: One hundred and seventy-eight patients were enrolled and followed up for a median (IQR) time of 9 (3-18) months (mean time follow-up: 33.1±13 months). Clinical remission was achieved in 57 (32.1%) patients: these patients continued with GOL, but only 6 patients (3.4%) were still under clinical remission with GOL at the 42nd month of follow-up. Clinical response occurred in 64 (36.4%) patients; colectomy was performed in 8 (7.8%) patients, all of them having primary failure. Steroid-free remission occurred in 23 (12.9%) patients, and mucosal healing was achieved in 29/89 (32.6%) patients. Adverse events occurred in 14 (7.9%) patients., Conclusions: Golimumab does not seem able to maintain long-term remission in UC in real life. The safety profile was good.

Objective: Ustekinumab (UST) is an anti-IL12/23 antibody for the treatment of Crohn's Disease (CD). The aim of this study was to compare the efficacy and safety of UST in a large population-based cohort of CD patients who failed previous treatment with other biologics., Patients and Methods: 194 CD patients (108 males and 86 females, mean age 48 years (range 38-58 years) were retrospectively reviewed. 147 patients were already treated with anti-TNFα (75.8%), and 47 (24.2%) patients were already treated with anti-TNFα and vedolizumab. Concomitant treatment with steroids was present in 177 (91.2%) patients., Results: At week 12, clinical remission was achieved in 146 (75.2%) patients. After a mean follow-up of 6 months, clinical remission was maintained in 135 (69.6%) patients; at that time, mucosal healing was assessed in 62 (31.9%) patients, and it was achieved in 33 (53.2) patients. Three (1.5%) patients were submitted to surgery. Steroid-free remission was achieved in 115 (59.3%) patients. Both serum C-Reactive Protein and Fecal Calprotectin (FC) levels were significantly reduced with respect to baseline levels during follow-up. A logistic regression, UST therapy as third-line therapy (after both anti-TNFα and vedolizumab), FC >200 µg/g, and HBI ≥8 were significantly associated with lack of remission. Adverse events occurred in 5 (2.6%) patients, and four of them required suspension of treatment., Conclusions: UST seemed to be really effective and safe in CD patients unresponsive to other biologic treatments, especially when used as second-line treatment.

Background & Aims: Several add-on devices have been developed to increase rates of colon adenoma detection (ADR). We assessed their overall and comparative efficacy, and estimated absolute magnitude of benefit through a network meta-analysis., Methods: We searched the PubMed/Medline and Embase database through March 2017 and identified 25 randomized controlled trials (comprising 16,103 patients) that compared the efficacy of add-on devices (cap; Endocuff; Arc Medical Design Ltd, Leeds, UK, and Endorings; Us Endoscopy, Mentor, OH) with each other or with standard colonoscopy. The primary outcome was ADR; secondary outcomes included rate of polyp detection, and rate of and time to cecal intubation. We performed pairwise and network meta-analyses, and appraised quality of evidence using Grading of Recommendations Assessment, Development and Evaluation. We estimated the magnitude of increase in ADR by low-performing endoscopists (baseline ADR, 10%) and high-performing endoscopists (baseline ADR, 40%) with use of these devices., Results: Overall, distal attachment devices increased ADR compared with standard colonoscopy (relative risk [RR], 1.13; 95% CI, 1.03-1.23; low-quality evidence), with potential absolute increases in ADR to 11.3% for low-performing endoscopists and to 45.2% for high-performing endoscopists. In a comparative evaluation, we found low-quality evidence that Endocuff increases ADR compared with standard colonoscopy (RR, 1.21; 95% CI, 1.03-1.41), with anticipated increases in ADR to 12% for low-performing endoscopists and to 48% for high-performing endoscopists. We found very low quality evidence to support the use of Endorings (RR, 1.70; 95% CI, 0.86-3.36) or caps (RR, 1.07; 95% CI, 0.96-1.19) vs standard colonoscopy for increasing ADR. The benefit of one distal attachment device over another was uncertain due to very low quality evidence., Conclusions: Based on network meta-analysis, we anticipate only modest improvement in ADRs with use of distal attachment devices, especially in low-performing endoscopists., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: The aim of this study was to assess the efficacy and safety of infliximab biosimilar (IFX) IFX CT-P13 in inducing and maintaining remission in ulcerative colitis (UC) outpatients in Italian primary gastroenterology centers., Methods: Patients were prospectively assessed at entry, after 8, 12, 24, 36, and therefore 52 weeks. Clinical activity was rated as per the Mayo Score. The primary endpoint was reaching of clinical remission (Mayo Score ≤2). Several secondary endpoints were clinical response to treatment, reaching of mucosal healing (MH), safety of the drug., Results: Twenty-nine patients (16 males and 13 females, mean age 45 years, range 35-42 years) were enrolled. Eleven (37.9%) patients had previous exposure to other anti-TNF-α. Clinical remission was present in 78.5% at week 24, and in 100% at 12-month follow-up. Subgroup analysis did not reveal significant differences in clinical remission between IFX-naïve patients and patients switching from originator to IFX biosimilar. A clinical response was observed in 92.3% at week 8, in 50.0% at week 16, in 100% at week 36 and in 100% at 12-month follow-up. MH occurred in 85.7% at week 24, and in 100% at 12-month follow-up Reduction of steroids was achieved in 92.3% at week 8, and in 100% during follow-up. One patient underwent proctocolectomy 3 weeks after starting IFX CT-P13. The median C-reactive protein and calprotectin levels during follow-up were significantly reduced during follow-up. No adverse events were observed during follow-up., Conclusions: IFX CT-P13 seems to be very effective and safe in real-life experience at primary IBD centers.

Background and Aims: Golimumab (GOL) has been recently approved in Italy for the treatment of ulcerative colitis (UC) unresponsive to standard treatments. Our aims were to assess the real-life efficacy and safety of GOL in managing UC outpatients in Italian primary Inflammatory Bowel Diseases (IBD) centres., Methods: Consecutive UC outpatients with at least 3-months follow-up were enrolled. Primary end-point was the induction and maintenance of remission in UC, defined as Mayo score

Aim: To assess the impact of short infliximab (IFX) infusion on hospital resource utilization and costs., Methods: All inflammatory bowel diseases (IBD) patients who received IFX 1 h infusion from March 2007 to September 2014 in eight centers from Southern Italy were included in the analysis. Demographic, clinical and infusion related data were collected. The potential benefits related to the short infusion protocol were assessed both in terms of time saving and increased infusion unit capacity. In addition, indirect patient-related cost savings were evaluated., Results: One hundred and twenty-five patients were recruited (64 with ulcerative colitis and 61 with Crohn's disease). Median duration of disease was of 53 mo and mean age of pts at diagnosis was of 34 years (SD: ± 13). Adverse infusion reactions were reported in less than 4% both before and after short infusion. The total number of infusions across the selected centers was of 2501 (30.5% short infusions). In the analyzed cohort, 1143 h were saved (762 in the infusion and 381 in observation phases) through the rapid IFX infusion protocol. This time saving (-15% compared to the standard protocol in infusion phase) represents, from the hospital perspective, an opportunity to optimize infusion unit capacity by allocating the saved time in alternative cost-effective treatments. This is the case of opportunity cost that represents the value of forgone benefit which could be obtained from a resource in its next-best alternative use. Hence, an extra hour of infusion in the case of standard 2-h IFX represents a loss in opportunity to provide other cost effective services. The analysis showed that the short infusion increased the infusion units capacity up to 50% on days when the IFX infusions were scheduled (infusion phase). Furthermore, the analysis showed that the short IFX infusion protocol leads to time savings also in the post-infusion phase (observation) leading to a time saving of 10% on average among the analyzed centers. Finally, the short infusion protocol has been demonstrated to lead to indirect cost savings of €138/patient (average -€17.300 on the whole cohort)., Conclusion: A short IFX infusion protocol can be considered time and cost saving in comparison to the standard infusion protocol both from the hospital's perspective, as it contributes to increase infusion units capacity, and the patients' perspective, as it reduces indirect costs and the impact of treatment on everyday life and work productivity., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interests. None of the authors have any financial or other relations that could lead to a conflict of interest.

Background: In recent years, the use of MRI in patients with Crohn's disease (CD) has increased. However, few data are available on how MRI parameters of active disease change during treatment with anti-TNF and whether these changes correspond to symptoms, serum biomarkers, or endoscopic appearance. The aim of this study was to determine the changes over time in MRI parameters during treatment with anti-TNF in patients with CD, and to verify the correlation between MRI score, endoscopic appearance and clinical-biological markers., Methods: We performed a prospective single centre study of 27 patients with active CD (18 males and 9 females; median age of 27,4 ys; age range, 19-49). All patients underwent ileocolonoscopy and MRI at baseline and 26 weeks after anti-TNF therapy. Endoscopic severity was graded according to the Simple Endoscopic Score for Crohn's Disease (SES-CD) and Magnetic Resonance Index of Activity (MaRIA) was calculated. Patients underwent clinical evaluation (CDAI) and the C-reactive protein (CRP) level was measured. The associations between variables were assessed with Pearson's bivariate correlation analysis., Results: A total of 135 intestinal segments were studied. The median patient age was 27,4 years, 67 % were male and the mean disease duration was 6,1 years. For induction of remission, 18 patients were treated with infliximab and 9 with adalimumab. The mean SES-CD and MaRIA scores significantly changed at week 26 (SES-CD: 14,7 ± 8,9 at baseline vs. 4,4 ± 4,6 at 26 weeks - p < 0.001; MaRIA: 41,1 ± 14,8 at baseline vs. 32,8 ± 11,7 at 26 weeks - p < 0.001). Also the CDAI and serum levels of CRP decreased significantly following treatment (p < 0.001). The overall MaRIA correlated with endoscopic score and with clinical activity (CDAI) both at baseline and at week 26 (p < 0.05). The correlation between overall MaRIA and CRP was significant only at week 26 (p < 0.001)., Conclusions: The MaRIA has a good correlation with SES-CD, a high accuracy for prediction of endoscopic mucosal healing and is a reliable indicator to monitor the use of TNF antagonists in patients with CD.

Background and Aim: Terminal ileum adenocarcinoma is a rare tumour. Its incidence or prevalence among the other sites of gastro-intestinal tract is unknown, since it has been only sporadically described. Since contrast enhanced ultrasonography has been recently used to study bowel alterations in the course of neoplastic or inflammatory disorders, we report here a case of a rare tumour (terminal ileum poorly differentiated adenocarcinoma) in which the investigation played a pivotal role to obtain a defined diagnosis. MATERIALS AND METHODS (CASE REPORT): Here we report the case of a 62 year old male patient. Due to intestinal occlusive symptoms and body weight decrease of about 8 Kg, he performed an abdominal computed tomography, intestinal magnetic resonance with double contrast medium, colonoscopy and contrast enhanced ultrasonography using a second generation medium., Results: In our case the peculiar aspect is that no arterial enhancement was observed and the finding remained unchanged for about 2.48 minutes as well as after a further administration of 1.5 ml of contrast medium. This aspect was not suggestive of an active inflammation such as Crohn's disease, where a marked contrast medium enhancement should be expected., Conclusions: At present it is too speculative to emphasize contrast enhanced ultrasonography as usefulness tool in the diagnosis of terminal ileum tumors. Nevertheless, our preliminary experience strongly encourages the diffusion of the method.

Background and Aims: Inflammatory bowel diseases (IBD) evoke a damage-repair process accompanied by the activation of apoptotic genes. Data on transglutaminase (TG) expression in apoptotic cells in inflamed colonic epithelium has not been reported, although TG cross-links proteins within typical apoptotic bodies in various cell lines. In an experimental model of colitis we investigated the expression of different markers of apoptosis related to the degree and development of colonic inflammation., Methods: Two studies were performed: (a) Colitis was induced by the administration of 2,4,6-trinitrobenzen sulfonic acid (TNBS) at a dose of 10 or 20 mg per rat in 50% ethanol, and the rats were killed 1 week later; (b) Colitis was induced by 20 mg TNBS and the rats were killed 3 days, 1, 2, and 4 weeks thereafter. The colon of rats was macroscopically assessed, and biopsies were histologically assessed and immunoprobed for FasL, FasR, p53 and tTG. Cell death was detected by TUNEL, and TG activity was assayed on colon homogenates., Results: Study A: According to enhanced TUNEL positivity, FasR/FasL and p53 expression increased depending on the severity of the colitis. Study B showed increased p53 expression at day 3 while FasR/FasL coexpression peaked at 1 week. In both studies tTG was mainly expressed in the extracellular matrix of damaged tissue and in the submucosa., Conclusions: Our findings suggest that expression of apoptosis markers is related to the degree of colitis and show that apoptosis is sustained by both p53 and FasR/FasL pathways, depending on the phase of colitis development. Moreover, the lack of TG staining in typical apoptotic bodies may account for a perturbation of the cross-linked apoptotic envelope that may be an important determinant in the development of immune response in ulcerative colitis., (Copyright 2004 Springer-Verlag)

Background and Aim: One-week triple therapy for Helicobacter pylori revealed, during these last few years, a decrease in the eradication rate, so that the prolongation of its duration has been proposed. A sequential scheme recently showed very satisfactory results. We performed a prospective randomised study with the aim of either evaluating whether the triple therapy prolongation may improve its effectiveness and comparing its outcome with that of sequential regimen., Patients and Methods: Three hundred and forty-two H. pylori positive patients completed the study. They were randomised to receive one of the following treatments: (i) a 7-day triple therapy comprising of rabeprazole (20 mg, b.i.d.) plus clarithromycin (500 mg, b.i.d.) and amoxycillin (1 g, b.i.d.); (ii) a 10-day triple therapy comprising the same scheme; (iii) a 10-day sequential regimen comprising of rabeprazole (20 mg, b.i.d.) plus amoxycillin (1 g, b.i.d.) for 5 days followed by rabeprazole (20 mg, b.i.d.) plus clarithromycin (500 mg, b.i.d.) and tinidazole (500 mg, b.i.d.) for the next 5 days. Therapeutic results were expressed using both intention-to-treat and per protocol analyses with 95% confidence intervals. A model of multivariate logistic regression analysis was performed using therapeutic outcome as a dependent variable and including endoscopic finding, smoking habit, age and sex as candidates for the model., Results: Sequential regimen showed a significant gain in the eradication rate as compared to the 7-day (P < 0.0001) and the 10-day (P < 0.01) triple therapies, respectively. Overall eradication was lower in smokers than in non-smokers, but the difference remained significant only in the 7-day triple therapy (P < 0.01). Additionally, the overall eradication was higher in peptic ulcer than dyspepsia (P < 0.01), even if this difference was significant only for both triple therapies., Conclusions: Seven-day triple therapy achieves disappointing eradication rates in dyspeptics and smokers. Prolonging triple therapy to 10 days does not significantly improve the eradication rate. The novel 10-day sequential regimen is more effective and equally tolerated than the 10-day triple therapy.

Background: Host response plays a major role in pathogenesis of Helicobacter pylori-induced gastroduodenal disease including adenocarcinoma of distal stomach. Epidermal growth factor-related growth factors are important modulators of gastric homeostasis in normal and damaged gastrointestinal mucosa., Aim: To evaluate expression of heparin binding epidermal growth factor and amphiregulin in antral mucosa of Helicobacter pylori-infected and non-infected dyspeptic patients and to correlate levels of heparin binding-epidermal growth factor and amphiregulin mRNA with mitogenic activity of gastric epithelial cells., Methods: A total of 10 Helicobacter pylori-infected and 15 Helicobacter pylori non-infected (10 with and 5 without gastritis) dyspeptic patients were studied. Diagnosis of Helicobacter pylori infection was based on rapid urease test and histology. Heparin binding-epidermal growth factor and amphiregulin mRNA expression in antral mucosa were assessed by reverse transcriptase-polymerase chain reaction. Protein expression and localization of both peptides were determined by immunohistochemistry. Mitogenic activity of antral gastric mucosa was assessed by determination of proliferating cell nuclear antigen labelling index by immunohistochemistry., Results: Heparin binding-epidermal growth factor and amphiregulin mRNA expression increased in Helicobacter pylori-infected vs Helicobacter pylori non-infected patients. Heparin binding-epidermal growth factor and amphiregulin immunostaining was more intense and deeper in gastric gland compartment in infected mucosa than in non-infected mucosa. Increase in heparin binding-epidermal growth factor and amphiregulin mRNA expression significantly correlated with increase in proliferating cell nuclear antigen labelling index., Conclusions: Helicobacter pylori gastritis is associated with up-regulation of heparin binding-epidermal growth factor and amphiregulin which correlates with increased mitogenic activity of gastric mucosa. Increased heparin binding-epidermal growth factor and amphiregulin expression is postulated to contribute to reparative response of gastric mucosa to Helicobacter pylori infection.

Background/aims: Tissue transglutaminase has been reported to be involved in the healing of experimental gastric ulcer; nevertheless, other type(s) of transglutaminase could be involved. The present experiments aimed at examining whether plasma transglutaminase (factor XIIIa) contributes to such healing and at evaluating whether factor XIII supplementation improves gastric mucosal lesions., Methods: The healing effect of 200 U/kg of factor XIII administered intravenously was examined using a water immersion restraint rat model of stress gastric damage. The rats were sacrified 0, 2, 4, and 12 h after stress. The gastric mucosa was examined macroscopically and microscopically, and the transglutaminase activities were assayed in serum and gastric mucosa. Factor XIIIa and tissue transglutaminase protein levels in the gastric mucosa were analyzed by immunoblot. Immunohistochemistry was used to identify the location of tissue transglutaminase, factor XIIIa, and fibronectin in the gastric mucosa., Results: The transglutaminase activity, reduced by stress in the gastric mucosa, increased up to 12 h after stress, peaking at 4 h, when the ulcer index significantly decreased. The serum transglutaminase level was low at all time points. Exogenous administration of factor XIII allowed a faster reduction of the ulcer index that was coincident with an increased transglutaminase activity in the mucosa. Both tissue transglutaminase and factor XIIIa protein levels were reduced by 6 h of stress and increased after factor XIII administration. Immunohistochemistry showed a colocalization of both factor XIIIa and tissue transglutaminase with fibronectin in the extracellular matrix of the damaged area., Conclusions: Two forms of transglutaminase are involved in the healing of stress-induced gastric erosions, and factor XIII administration allows faster gastric mucosa healing.

During inflammatory colitis in man and experimental animals, the production of free radicals increases. This study evaluated the histological pattern and biochemical parameters of oxidative damage during acute and chronic colitis induced by 2,4,-trinitrobenzenesulfonic acid + ethanol in rats. On the samples of scraped mucosa of six groups of rats, one not treated, one killed after 1 hr, and those killed one, two, four, and eight weeks after the induced-damage, we determined the histological and superoxide dismutase activity and the concentration of lipoperoxides, malonyldialdheyde, and reduced glutathione. After 1 hr, the mucosal damage and superoxide dismutase activity were slight; glutathione, lipoperoxides, and malonyldialdheyde were significantly increased. At one week, the histological damage was severe, decreasing progressively, and significantly correlated to superoxide dismutase activity. Lipoperoxides and malonyldialdheyde were high throughout the study. Glutathione was significantly increased at one and two weeks and dramatically decreased thereafter. Therefore, in experimental colitis the cascade of free-radical production induces a constant self-maintaining lipoperoxidation and consumes the cellular antioxidant capability.